Those who have irregular blood glucose concentration levels are medically required to regularly self-monitor their blood glucose concentration level. An irregular blood glucose level can be brought on by a variety of reasons including illness such as diabetes. The purpose of monitoring the blood glucose concentration level is to determine the blood glucose concentration level and then to take corrective action, based upon whether the level is too high or too low, to bring the level back within a normal range. The failure to take corrective action can have serious implications. When blood glucose levels drop too low—a condition known as hypoglycemia—a person can become nervous, shaky, and confused. Their judgment may become impaired and they may eventually pass out. A person can also become very ill if their blood glucose level becomes too high—a condition known as hyperglycemia. Both conditions, hypoglycemia and hyperglycemia, are potentially life-threatening emergencies.
Common methods for monitoring a person's blood glucose level are invasive in nature. Typically, to check the blood glucose level, a drop of blood is obtained from the fingertip using a lancing device. The blood drop is produced on the fingertip and the blood is harvested using a test sensor which is inserted into a testing unit. The test sensor draws the blood to the inside of the test unit which then determines the concentration of glucose in the blood.
One problem associated with this type of analysis is that there is a certain amount of pain associated with the lancing of a finger tip. Diabetics must regularly self-test themselves several times per day. Each test requires a separate lancing, each of which involves an instance of pain for the user. Further, each lancing creates a laceration in the users skin which take time to heal and are susceptible to infection just like any other wound.
Other techniques for analyzing a person's blood glucose level are noninvasive in nature. Commonly, such techniques interpret the spectral information associated with light that has been transmitted through or reflected from a person's skin. An advantage of this type of noninvasive analysis is that there is no associated pain or laceration of the skin. However, thus far, such techniques have proven unreliable because many techniques fail to recognize the many issues that impact the analysis. For example, many noninvasive reflectance and transmission based systems do not account for the fact that the obtained spectral data contains glucose information from the portion of body tissue being analyzed as a whole, and is not limited to blood glucose. Other techniques do not account for irregularities in the spectral signal of the analyte due instrumental drift, temperature changes in the tissue under analysis, spectral characteristics of the tissue that change due to pressure changes, etc. that can occur during the analysis or between analyses. These irregularities can impact the quality of the calibration model or the algorithms that are used to determine the analyte concentrations from the noninvasively collected spectral data. The spectral data that has these irregularities cannot be used by the algorithms to determine the analyte concentrations.
Accordingly, there exists a need for a reliable noninvasive system for the determination of analytes in body fluids.
Near infrared radiation has been applied non-invasively in attempts to identify the glucose content of a patient's blood. However, non-invasive methods subject to the infrared radiation areas of the body that contain blood vessels, but other fluids containing glucose are present. A person's skin contains glucose in the extracellular fluid, which includes plasma and interstitial fluid. Since measurements of glucose by non-invasive methods are made in the dermis, they primarily determine the glucose in the extracellular fluid, plus some glucose in blood contained in capillaries in the skin. What is wanted is a correlation with the glucose content of blood, typically a small amount in the general range of 50 to 450 mg/dL. Now, it will be evident that if absorption of infrared radiation at specific wavelengths that are associated with glucose could be detected and measured, then the desired information will have been obtained. In practice, the presence of water and other materials that absorb infrared radiation make it difficult to measure the amount of glucose in the blood that is present and exposed to the infrared radiation. Some research has been directed to comparing the absorption of infrared radiation at certain wavelengths with a reference beam that has not been directed to the skin of a subject. More commonly, attempts have been made to correlate the response of a subject to a broadband of infrared radiation with measurements made by reliable methods of determining the glucose content of blood obtained by invasive methods.
In some patents including U.S. Pat. Nos. 5,435,309 and 5,830,132, methods are described in which, rather than applying a broadband of radiation or pre-selected wavelengths, a band of infrared radiation is scanned using acousto-optic tunable filters (AOTF). These solid state devices permit rapid scanning of a band of radiation without using filters or moving parts. The response of the subject to the radiation is detected and correlated using techniques familiar to those skilled in the art such as, for example, partial least squares (PLS) and principal component analysis (PCA).
In co-pending U.S. patent application Ser. No. 10/361,895 published as U.S. 2004/0092804A1, an improved method of measuring glucose non-invasively that employs AOTF was disclosed. In addition to an algorithm developed to correlate the spectral information with direct measurements of glucose in a subject's blood, the system employed several unique features that improved accuracy and consistency. Those features included a clamping device for assuring good contact with body tissue and which provided precise temperature and pressure control at the point of measurement. A unique attachment clamping device, including sapphire rods, termed an optoid by the inventors, were provided to direct radiation into the measurement region and transmit light leaving the region to the radiator detector. The device represented an advance in the art, but further improvement was sought by the present inventor.
It will be evident from the above discussion that obtaining accurate measurements of small amounts of glucose in blood by non-invasive methods is difficult since the concentration of glucose is small relative to other materials in the sample area and its response to infrared radiation occurs in regions in which other materials in higher concentrations also respond. At least two important problems are involved. First, much of the incident radiation is absorbed or scattered and the amount actually received by the detector is small. Thus, improving the signal-to-noise ratio is important. Second, water is present in large amounts relative to glucose and interferes with accurate measurement of glucose. This is especially a problem with instruments that employ a wide band of infrared radiation such as scanning and diode array instruments. As discussed above, instruments using AOTF scan a predetermined radiation band. This makes possible adjusting the power of the monochromatic light provided by the AOTF device so that the signal received at pre-selected wavelengths is maximized across the entire spectral region. Due to the different absorbency and scattering characteristics of the skin in the infrared region, the spectrum collected from the skin can have orders of magnitude differences in intensity. The limitations of most systems are that they are not able to maximize the information quality across such a divergent spectral region. Improvement of the signal-to-noise ration would be advantageous. Varying skin characteristics that affect scattering and absorbance of infrared radiation can be accounted for and then the signal-to-noise ratio could be improved. Another improvement in an AOTF device would provide feedback to adjust the power and the scanning time to provide the most accurate results. Further improvement could be obtained by programming the AOTF to change the amplitude of the radiation in specific regions of the spectrum that are obtained from an interaction with a known glucose concentration. The information so obtained would help to characterize the scattering, absorbance, and interference effects associated with a pure glucose sample.
The present inventor has found that an improved non-invasive glucose-measuring instrument can be made employing the above-described principles. Such an improved instrument will be described in detail below. Furthermore, the principles employed in the glucose-measuring instrument may be applied more generally to measuring analytes in may other instances.